Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002535841 | SCV003472637 | likely pathogenic | Exostoses, multiple, type 2 | 2023-03-23 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 608 of the EXT2 protein (p.Tyr608Cys). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXT2 protein function. ClinVar contains an entry for this variant (Variation ID: 638619). This missense change has been observed in individual(s) with autosomal recessive EXT2-related conditions (PMID: 30288735). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). |
| OMIM | RCV000791304 | SCV000930615 | pathogenic | Seizures-scoliosis-macrocephaly syndrome | 2019-08-02 | no assertion criteria provided | literature only |